Many common disorders of the nervous system are potentially treatable using techniques that employ precise, controlled electrical recording (for localization) and/or precise, controlled electrical stimulation (for modulation). An example is deep brain stimulation (DBS) for movement disorders (e.g. Parkinson's disease, which affects 1 million Americans). DBS is currently in clinical trials for conditions such as intractable epilepsy, depression, and eating disorders. Precise localization within the brain will also be essential for implantation of stem cells and other forms of transplantation when such methods reach clinical usefulness. Nanoelectrodes offer the possibility of improving significantly our ability (1) to localize specific regions (subnuclei) of the brain, with the benefit of permanent implantation (which is not feasible in clinical situations with current microelectrodes), (2) to stimulate specific regions (subnuclei) of the brain much more precisely than is possible with current macroelectrodes, and (3) to monitor or record the local environments (neurotransmitter levels, e.g. dopamine and glutamate) with nanomolar sensitivity and millisecond temporal resolution yet with minimum disturbance using in situ electrochemical methods based on nanoelectrode arrays. The long-term goal is to establish a permanently-implanted closed-loop system where the monitoring of neurotransmitter levels and local brain electrical activity guides the local brain stimulation (neuromodulation). The proposed work involves the development of nanoelectrode arrays specifically for precise, permanently implanted, local brain recording of electrical activity and neurotransmitter levels as well as stimulation. Following additional refinement and laboratory testing of 200 #m nanoelectrode arrays already developed, the porposed research utilizes cell cultures, brain tissue slices, and a standard small animal model of Parkinson's disease to test the prototype nanoelectrode arrays. This research plan extends and integrates the work done to date by the Nanotechnology and Smart Systems groups at NASA Ames Research Center: (1) nanoelectrode fabrication and application to the development of ultrasensitive biosensors, and (2) real-time tissue recognition using multiple microsensors and neural networks to determine a unique "signature" for both tissues (normal and abnormal) and regions (subnuclei) of the brain.